Galactokinase deficiency: lessons from the GalNet registry

Genet Med. 2021 Jan;23(1):202-210. doi: 10.1038/s41436-020-00942-9. Epub 2020 Aug 18.


Purpose: Galactokinase (GALK1) deficiency is a rare hereditary galactose metabolism disorder. Beyond cataract, the phenotypic spectrum is questionable. Data from affected patients included in the Galactosemias Network registry were collected to better characterize the phenotype.

Methods: Observational study collecting medical data of 53 not previously reported GALK1 deficient patients from 17 centers in 11 countries from December 2014 to April 2020.

Results: Neonatal or childhood cataract was reported in 15 and 4 patients respectively. The occurrence of neonatal hypoglycemia and infection were comparable with the general population, whereas bleeding diathesis (8.1% versus 2.17-5.9%) and encephalopathy (3.9% versus 0.3%) were reported more often. Elevated transaminases were seen in 25.5%. Cognitive delay was reported in 5 patients. Urinary galactitol was elevated in all patients at diagnosis; five showed unexpected Gal-1-P increase. Most patients showed enzyme activities ≤1%. Eleven different genotypes were described, including six unpublished variants. The majority was homozygous for NM_000154.1:c.82C>A (p.Pro28Thr). Thirty-five patients were diagnosed following newborn screening, which was clearly beneficial.

Conclusion: The phenotype of GALK1 deficiency may include neonatal elevation of transaminases, bleeding diathesis, and encephalopathy in addition to cataract. Potential complications beyond the neonatal period are not systematically surveyed and a better delineation is needed.

Keywords: GALK1 gene variants; neonatal complications; cataract; galactosemias registry; galactokinase 1 deficiency.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cataract*
  • Galactokinase / deficiency*
  • Galactokinase / genetics
  • Galactosemias* / epidemiology
  • Galactosemias* / genetics
  • Homozygote
  • Humans
  • Infant, Newborn
  • Registries


  • GALK1 protein, human
  • Galactokinase